An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis

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Title: An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis
Author(s): Vassos, E
Di Forti, M
Coleman, J
Iyegbe, C
Prata, D
Euesden, J
O'Reilly, P
Curtis, C
Kolliakou, A
Patel, H
Newhouse, S
Traylor, M
Ajnakina, O
Mondelli, V
Marques, TR
Gardner-Sood, P
Aitchison, KJ
Powell, J
Atakan, Z
Greenwood, KE
Smith, S
Ismail, K
Pariante, C
Gaughran, F
Dazzan, P
Markus, HS
David, AS
Lewis, CM
Murray, RM
Breen, G
Item Type: Journal Article
Abstract: Background Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses. Methods The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis. Results PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10−6), but lower in individuals of African ancestry (R2 = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2 = 9.2%, p = .002). Conclusions PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP.
Publication Date: 15-Mar-2017
Date of Acceptance: 22-Jan-2016
URI: http://hdl.handle.net/10044/1/54563
DOI: https://dx.doi.org/10.1016/j.biopsych.2016.06.028
ISSN: 0006-3223
Publisher: Elsevier
Start Page: 470
End Page: 477
Journal / Book Title: Biological Psychiatry
Volume: 81
Issue: 6
Copyright Statement: © 2016 Society of Biological Psychiatry. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Science & Technology
Life Sciences & Biomedicine
Neurosciences
Psychiatry
Neurosciences & Neurology
Genetics
GWAS
Polygenic score
Psychosis
Risk prediction
Schizophrenia
GENOME-WIDE ASSOCIATION
RANDOMIZED CONTROLLED-TRIAL
1ST EPISODE PSYCHOSIS
COMPLEX DISEASES
PSYCHIATRIC-DISORDERS
FAMILY-HISTORY
SOUTH LONDON
SCHIZOPHRENIA
POPULATION
AFRICAN
GWAS
Genetics
Polygenic score
Psychosis
Risk prediction
Schizophrenia
Adult
African Continental Ancestry Group
Case-Control Studies
European Continental Ancestry Group
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Multifactorial Inheritance
Psychotic Disorders
Risk Factors
Schizophrenia
Young Adult
Humans
Genetic Predisposition to Disease
Risk Factors
Case-Control Studies
Psychotic Disorders
Schizophrenia
Genotype
Multifactorial Inheritance
Adult
African Continental Ancestry Group
European Continental Ancestry Group
Female
Male
Young Adult
Science & Technology
Life Sciences & Biomedicine
Neurosciences
Psychiatry
Neurosciences & Neurology
Genetics
GWAS
Polygenic score
Psychosis
Risk prediction
Schizophrenia
GENOME-WIDE ASSOCIATION
RANDOMIZED CONTROLLED-TRIAL
1ST EPISODE PSYCHOSIS
COMPLEX DISEASES
PSYCHIATRIC-DISORDERS
FAMILY-HISTORY
SOUTH LONDON
SCHIZOPHRENIA
POPULATION
AFRICAN
06 Biological Sciences
17 Psychology And Cognitive Sciences
11 Medical And Health Sciences
Psychiatry
Publication Status: Published
Appears in Collections:Clinical Sciences
Imaging Sciences
Faculty of Medicine



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